One of the major challenges for performing cell based screening is the isolation of small populations of cells in a manner that allows for subsequent screening procedures. Traditional devices and methods of isolating cells do not adequately provide for the isolation of small populations of cells without performing steps that potentially modify cellular function or activity. Isolation of cells is not only important in screening, but also in processes that involve the monitoring, measuring, and/or use of the output of cellular activity or function (e.g. antibody production) for small populations of cells.
For example, with respect to antibody production, one of the approaches used to produce antibodies is to manufacture hybridomas. These are cells created by the fusion of antibody-secreting B-cells and myeloma cells. This method is variable with respect to almost all stages of the process including the duration of screening and required needs for cell growth and proliferation. Much of the variability can be attributed to the immunogen and immune response mounted by the immunized animal. Moreover this process is time consuming and labor intensive.
In general, once the fusion is performed and the cells are plated, there are several issues that have to be addressed. First, the cells will grow at different rates, thus the point at which one must perform the assay for antibody production to assess positive pools of cells can vary and may require more than one assay point on the same pool of cells. During this process, the rapidly growing cells need to be passaged in order to promote viability and to prevent loss of potentially positive clones. The next step is to perform limiting dilution with the goal of achieving clonal populations. Successive rounds of this process may be required to achieve clonal or near clonal populations.
The value of specific monoclonal antibodies as useful tools for diagnostics and immuno-therapies has meant that investigators have had no alternative but to tolerate long production periods and high development costs. Rapid and efficient ways of screening hybridoma cell lines for antibody production are not presently available. Therefore, there is a need for methods and devices to accelerate monoclonal antibody production for experimental, diagnostic and therapeutic applications. The devices and methods disclosed herein dramatically shorten the period for monoclonal antibody production from a period of weeks to a period of days. The invention provides a multicomponent device that also has application for other cell types requiring the isolation of a small population of cells and requiring the subsequent clonal expansion of this population of cells.